Analysis and control of aerosol flow

ABSTRACT

An aerosol generation system has a light source arrangement which provides signals at first and second wavelengths, and the detected light signals are recorded. The detected signals are processed to derive at least a measure of the aerosol particle size. This can be used in combination with the other parameters which are conventionally measured, namely the aerosol density and flow velocity. Thus, optical measurement (possibly in combination with an air flow measurement) can be used to estimate the aerosol output rate as well as the particle size.

CROSS-REFERENCE TO PRIOR APPLICATIONS

This application is the U.S. National Phase application under 35 U.S.C.§371 of International Application Serial No. PCT/IB2012/055825, filed onOct. 23, 2012, which claims the benefit of U.S. Application Ser. No.61/552,507, filed on Oct. 28, 2011. These applications are herebyincorporated by reference herein.

TECHNICAL FIELD OF THE INVENTION

This invention relates to the analysis of an aerosol flow.

BACKGROUND TO THE INVENTION

A nebulizer is a drug delivery system by aerosol into the lungs, and isused to treat diseases such as Cystic Fibroses, COPD and Asthma. Anumber of companies make devices for respiratory drug delivery byaerosol. Preferably the devices are compact, portable, battery operatedand lightweight.

Nebulizers generate an aerosol flow, and the patient receives a specificamount of medication in the form of small droplets (aerosol) that aretypically formed by forcing the medication through a mesh in the form ofa thin metal plate with tiny holes.

The volume of medication to be nebulized (typically 0.2 to 2 ml) isdosed into the device, and the device generates the aerosol by means ofwell known methods such as a vibrating mesh as mentioned above, or avibrating horn, or vibrating flat plate in a resonant cavity. Therequired ultrasonic vibration is generated by an actuator, typically apiezoelectric crystal. The amount of medication that reaches the patientduring the treatment is equal to the supplied medication dose minus theaerosol deposited in the device and residues of medication that remainin the device after the treatment is finished.

The proper medical dosage of a nebulizer is essentially dependent on theoutput volume, but correct application of the dose can also depend onthe particle size of the aerosol in which the drug is dissolved. Theoutput volume varies with aging of the output mesh of the nebulizerbecause the mesh will deteriorate over time, for example due to cloggingof the thousands of tiny holes (˜2.5 micron diameter conical holes). Theviscosity of the medicine may also change with temperature, and hencechange the output.

The breathing pattern of the patient is also of importance. In currentsystems, aerosol density and particle size are not measured, let aloneused to give feedback to the system or patient. This may lead to underdosage, over dosage, waste of drug, unnecessary contamination of theenvironment and higher costs.

For a medication therapy, it is sometimes required that not only thedose is precisely defined, but also the rate at which the medication isdelivered, namely the aerosol output rate. The nebulizer generallycontrols the aerosol output rate by means of the electrical power anddriving frequency applied to the piezoelectric drive system.

The aerosol output rate cannot be exactly predicted based on the appliedelectrical power. Aerosol generating systems may have differentefficiencies (amount of aerosol generated per unit electrical power),for example due to device and mesh tolerances, temperature, andcleanliness of the mesh.

A system has been proposed that estimates the aerosol output rate bymeasuring the density of the aerosol beam, which is then used in afeedback control loop to adjust the electrical power. The aerosoldensity can be measured by means of an optical beam perpendicular to theaerosol beam. The optical beam can be generated by a light emittingdiode (LED). The beam shape of the light from a LED is divergent, andthe optical beam may be collimated to a parallel or nearly parallel beamusing one or more lenses or mirrors. The beam may be further shapedusing a circular or rectangular diaphragm.

The optical beam crosses the aerosol beam, and falls on an opticalsensor (optionally through a diaphragm and optionally focused using oneor more lenses). The optical system can be calibrated by measuring thesensor signal at a time that no aerosol is present with the LED off(“dark signal”) and with the LED on (“light signal”). If the aerosolbeam is present, the rays of the optical beam are scattered by thedroplets, thus decreasing the light that falls on the optical sensor,and hence decreasing the measured output signal at the optical sensor.The decrease of light on the sensor caused by droplets in the light pathis called obscuration. The obscuration can be quantitatively expressedby the parameter (“light signal”−“measured signal”)/(“lightsignal”−“dark signal”).

The obscuration is a function of the droplet density in the aerosol beamand the length over which the light travels through the aerosol beam. Ifthe velocity of the aerosol beam is known, e.g. through a separate airflow rate measurement (using a differential pressure sensor or a flowsensor), then the aerosol output rate can be computed from the aerosoldensity and the volume of the aerosol beam that passes the optical beamper unit of time. The volume can be calculated from the product of thecross-sectional area of the aerosol beam and the velocity of the aerosolbeam.

The level of obscuration by itself does not give any indication ofaerosol density nor particle size. Only if the particle size is knowncan the aerosol density be derived from the obscuration. In practice,the nominal particle size is often mostly predetermined by the designand construction of the complete aerosol generator.

However, it is desirable to know the particle size, either to give anindication of the performance of the aerosol generating system (forexample to provide an indication of ageing) or because certain particlesizes are desired for particular absorption characteristics, so thatparticle size becomes a parameter which characterizes the performance ofthe system.

SUMMARY OF THE INVENTION

According to the invention, there is provided an aerosol generationsystem, comprising:

a flow device for generating an aerosol flow;

a light source arrangement and a light detector for detecting lightwhich has interacted with the aerosol flow;

a controller for controlling the light source arrangement and forinterpreting the detected light signals;

wherein the controller is adapted to:

control the light source arrangement to provide a first signal at afirst wavelength and to record a first detected light signal;

control the light source arrangement to provide a second signal at asecond wavelength and to record a second detected light signal;

process the first and second detected signals to derive a measure of theaerosol particle size.

The invention is based on the recognition that light sensing can be usedto derive a particle size parameter of the aerosol flow, as well as theconventional derivation of particle density (otherwise known as thevolume fraction). In particular, by providing measurement with at leasttwo wavelengths, the extra degree of freedom enables the particledensity as well as the particle size to be determined.

The light detector can be for detecting light which has passed throughthe aerosol flow, thus measuring obscuration. In this case, a dye can beadded to the aerosol liquid to increase the absorption and therebyincrease the signal strength.

Alternatively, the light detector can be for detecting light which hasbeen reflected or scattered by the aerosol flow. In this case, afluorescent additive can be added to the aerosol liquid, which isexcited by the light source light, again to increase the signalstrength. The absorption and scattering approaches can be used incombination.

The controller can be further adapted to derive the aerosol density fromthe detected light signals. Thus, the system can provide density andparticle size information.

The light source arrangement can comprise light sources at differentpositions along the aerosol flow, and a detector is then provided foreach light source, wherein the controller is adapted to derive theaerosol velocity from the detected light signals at the differentpositions along the aerosol flow. A cross correlation can be applied tothe signals received at the different positions along the aerosol flowwith a variable time delay, thereby to determine a time delay of theaerosol flow between the different positions. This then enables thevelocity to be measured.

The light detector can be adapted to separate polarized and depolarizedlight contributions to determine an amount of scattering.

A flow device controller can be used for controlling the flow device,and the system can comprise a feedback loop such that the flow devicecontroller takes account of monitored parameters (particle size andoptionally one or more of particle density and flow velocity) of theaerosol flow. The flow device control can be based on the electric powerand/or duty cycle.

The invention also provides a method of generating an aerosol,comprising:

generating an aerosol flow;

controlling a light source arrangement to provide a first signal at afirst wavelength and recording a first detected light signal;

controlling the light source arrangement to provide a second signal at asecond wavelength and recording a second detected light signal;

processing the first and second detected signals to derive a measure ofthe aerosol particle size.

BRIEF DESCRIPTION OF THE DRAWINGS

Examples of the invention will now be described in detail with referenceto the accompanying drawings, in which:

FIG. 1 shows an example of aerosol generation system of the invention;

FIG. 2 shows how the aerosol flow interacts with the light detectionsystem;

FIG. 3 shows the an electrical circuit for controlling a light sourceand associated detector;

FIG. 4 is used to explain how transmission through the aerosol isdependent on the flow rate;

FIG. 5 is used to explain how scattering from the aerosol is dependenton the flow rate;

FIG. 6 shows how various parameters vary with particle size;

FIG. 7 shows how different wavelengths of light give obscurationprofiles with respect to particle size that are different; and

FIG. 8 shows how different particle sizes give different relative volumeand obscuration.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

The invention provides an aerosol generation system in which a lightsource arrangement provides signals at first and second wavelengths, andthe detected light signals are recorded. The detected signals areprocessed to derive at least a measure of the aerosol particle size.This can be used in combination with the other parameters which areconventionally measured, namely the aerosol density and flow velocity.Thus, optical measurement (possibly in combination with an air flowmeasurement) can be used to estimate the aerosol output rate as well asthe particle size.

FIGS. 1 and 2 show an example of system of the invention. In FIG. 1, thesystem of the invention is combined with a system able to carry out aperformance test. The system may be external to or internal to anebulizer.

The system comprises an aerosol generator 1, which is for example apiezoelectric driven aerosol generation system 1, and a controller 9.The aerosol 2 is generated using a mesh. An optical system generates abeam (see, e.g., beam paths 3 _(A), 3 _(B), and 3 _(C)) at distance fromthe mesh.

FIG. 1 shows three possible beam paths, as 3 _(A), 3 _(B), and 3 _(C).

The optical system consists of a light source 6 (for the three possiblebeam configurations, the light source is shown as 6 _(A), 6 _(B) and 6_(C)) with optional lens and diaphragm, and an optical detector 8 (forthe three possible beam configurations, the light detector source isshown as 8 _(A), 8 _(B) and 8 _(C)) with optional lens and diaphragm. Inthe illustrated embodiment, communication takes place between controller(9), light source(s) (6, 6 _(A), 6 _(B) and 6 _(C)), light detector (8,8 _(A), 8 _(B) and 8 _(C)), and aerosol generation system 1 in afeedback loop fashion as shown.

The first beam path 3 _(A) between the light source 6 _(A) and detector8 _(A) is perpendicularly across the aerosol flow. The second beam path3 _(B) between the light source 6 _(B) and detector 8 _(B) involves theintroduction of the light signal in the direction of flow, using a firstreflector to redirect the light into a transverse direction, and using asecond reflector to redirect the light again parallel to the flowdirection to the sensor.

The third beam path 3 _(C) between the light source 6 _(C) and detector8 _(C) involves the introduction of the light signal diagonally into theaerosol flow, with reflection or scattering detected by the sensor.

The different flow paths are provided within a flow tube 10.

FIG. 1 also shows performance test equipment in the form of a filter 12,flow meter 14 and pump 16. These are not part of the nebulizer, but partof the experimental set up. Typically, in normal use the pump 16 isreplaced by the lungs of the patient.

The system may use one or more of the beam paths shown in FIG. 1.

The aerosol generation system 1 is driven by a signal from a drivecircuit. The drive signal may be a high frequency signal that ismodulated at a lower frequency. The output power may be controlled byeither the amplitude of the signal, the duty cycle of the modulation, orboth.

The output power of the drive circuit is set by an input signal from apower control feedback system (not shown).

If the light path is internal to the nebulizer, this allows for a blankintensity calibration when the aerosol generator is switched off.

The system of FIG. 1 is for implementing optical aerosol densitymeasurements (nephelometer) and additionally to provide particle sizeinformation.

FIG. 2 shows the optical set up for path A as a cross section throughthe mouth piece section, directly across the aerosol. In addition, FIG.2 shows an arrangement in which transmission as well as reflection ismonitored.

For this purpose, there is one detector 6 _(A). One emitter 8 _(A1) isplaced opposite to the detector for transmission measurements. Anotheremitter 8 _(A2) is placed next to the detector, but with a light shield20 between. This is used for reflection measurements. The light shieldreduces direct coupling of light into the detector.

FIG. 3 shows the electrical circuit diagram, for one light source anddetector pair.

The LED IR emitter 30 for example has a peak wavelength of 880 nm. Atypical example of the radiant flux is 23 mW at 100 mA forward current.The radiant intensity in the axial direction typically 7 mW/sr. Only oneemitter circuit is shown in FIG. 3 (the emitter, a drive transistor 30,a dc voltage source and a load resistor), but there will be two suchcircuits to implement the two emitters shown in FIG. 2. Furthermore,there are multiple emitter and detector circuit combinations to provideoperation at different frequencies, as explained further below.

The detector 32 is a photo diode, tuned to have the peak sensitivity atthe emitter wavelength (880 nm). A typical sensitivity is 0.65 A/W, andan active area 2.65×2.65 mm

The detector output in the form of a photocurrent is integrated by anintegrator 34. An A/D converter 36 detects the slope of the voltage onthe integrator, which is proportional to the amount of light. This canfor example comprise a 16 bit Sigma Delta A/D converter embedded in amicrocontroller.

Calibration measurements are carried out before system operation. Thesewill depend on the optical path being used. For the arrangement of FIG.2, a dark measurement of the photo diode is recorded, with the emittersoff. A transmission reference measurement involves measuring thetransmission without aerosol present, but with the transmission emitter8 _(A1) on. A reflection reference measurement involves measuring thereflection without aerosol present, but with the reflection emitter 8_(A2) on. These three measurements are all used for calibrationpurposes.

The signal measurement comprises a transmission measurement in which thetransmission through the aerosol is measured and a reflectionmeasurement in which the reflection by the aerosol is measured.

A measurement procedure comprises:

Perform dark measurement;

Perform transmission reference measurement, subtract dark measurement toderive a first transmission value Tr;

Perform reflection reference measurement, subtract dark measurement toobtain a first reflection value Rr;

Switch on aerosol generator;

Perform dark measurement;

Perform transmission measurement, subtract dark measurement to derive asecond transmission value T;

Perform reflection measurement, subtract dark measurement to derive asecond reflection value R.

The transmission level is then interpreted as Transmission=T−Tr and thereflection level is interpreted as Reflection=R−Rr. These values canthen be used to derive aerosol density information (in known manner) andcan be combined with flow velocity to derive output rate (again in knownmanner).

FIG. 4 shows the optical transmission percentage (with respect to aclear path) versus aerosol output rate.

The aerosol output rate and aerosol density scale linearly with eachother. All aerosol comes through the same channel at any time, so thesetting of pump speed (as part of the testing process) determines thedilution of the aerosol with air and hence determines the ratio betweenaerosol density and aerosol output.

FIG. 5 shows the backscattering efficiency as a function of aerosoloutput rate in arbitrary units.

FIGS. 4 and 5 show the result of the test set up, and show that theinvention can work.

The optical detector information does not give any indication of theparticle size. To explain how the invention enables particle size to bedetermined, analysis based on scattering theory is required.

Diffusively scattering media, such as milk, mist or (white) paint, alsocalled “diffusers”, “random media” or “turbid media”, are characterizedby at least four parameters (reference is made to “Miniaturized multipleFourier-horn ultrasonic droplet generators for biomedical applications”by Chen Tsai et al, Lab Chip 2010, 10, pp 2733-2740 and H. C. van deHulst, “Light scattering by small particles”, (Dover, N.Y., 1981)):

The so-called extinction length l_(ext), which is the characteristic forloss of intensity in the directly transmitted (unscattered) light: I=I₀exp(−z/l_(ext)) due to both absorption and scattering, where I₀ is theincident intensity. For substantially white (non-absorbing) medial_(ext) should be replaced with l_(sca), the scattering mean-free path;

The so-called transport mean-free path l_(tra) (sometimes also referredto as the reduced scattering length), which is the effective diffusionlength in the bulk of the scattering medium. It is the characteristiclength over which the light loses correlation with its originalpropagation direction;

The absorption length l_(abs), which is indicative of the “whiteness” ofthe medium;

The size or thickness d of the medium.

The difference between the scattering mean free path l_(sca) andtransport mean free path l_(tra) is a consequence of anisotropicscattering. The following relation holds:l _(tra) =l _(sca)/(1−

cos θ

)where θ is the scattering angle. If the particles scatter equal amountsof light in all directions then the mean cosine of the scattering angleis zero and hence l_(tra)=l_(sca).

In the above, the (statistical) homogeneity of the medium in both spaceand time is assumed. All parameters mentioned relate in some way oranother to the optical density of the medium. In a statisticallyhomogeneous medium of volume V, the following relations hold (in which ris the particle radius, n the particle refractive index, n_(med) therefractive index of the medium, λ the wavelength in vacuum, N the numberof particles and n₀=N/V the number density of particles):

volume fraction: f=4πr3n₀/3, 0<f<1, typically for packed spheres f<0.74

size parameter: x=2πr n_(med)/λ

geometric cross section: σ_(geo)=πr²

scattering cross section: σ_(sca)

absorption cross section: σ_(abs)

total cross section or extinction cross section: σ_(ext)=σ_(sca)+σ_(abs)

extinction length: l_(ext)=(n₀σ_(ext))⁻¹

particle “whiteness” or albedo: a=σ_(sca)/σ_(ext)

quality factor for scattering: Q_(sca)=σ_(sca)/σ_(geo)

scattering mean free path: l_(sca)=(n₀σ_(sca))⁻¹

scattering coefficient: μ_(s)=1/lsca

inelastic length:l_(in)=al_(sca)/(1−a)=l_(ext)/(1−l_(ext)/l_(sca))=(l_(ext) ⁻¹−lsca⁻¹)⁻¹

cross section for radiation pressure: σ_(pr)

quality factor for momentum transfer: Q_(pr)=σ_(pr)/σ_(geo)

transport mean free path: l_(tra)=(n₀σpr)⁻¹

reduced scattering coefficient: μs′=l/l_(tra)

attenuation length:l_(att)=l_(tra)/√(3(1−a)l_(tra)/(al_(sca)))=√(l_(tra)l_(in)/3)

absorption coefficient: μ_(a)=μ_(s)(1−a)/a

attenuation coefficient:κ=√(3μ_(a)μ_(s)′)=√(3(1−a)/(al_(sca)l_(tra)))=√(3μ_(s)′(l_(ext)⁻¹lsca⁻¹))

FIG. 6 shows the extinction efficiency Q_(ext) and the efficiency ofradiation pressure Q_(pr) of water droplets (refractive index 1.33) inair (refractive index 1) as a function of size. This can be calculatedby Mie theory, which provides an exact description of electromagneticscattering from spherical objects.

The extinction efficiency initially rises rapidly with the sizeparameter

, has several maxima and minima and tends asymptotically to a constantwith a decaying oscillation. The graphs in FIG. 6 represent the case ofweak absorption (imaginary part of refractive index k=0 and albedo a=1),where Q_(ext)=Q_(sca), but rigorous calculation of the scatteringproperties at wavelengths at which water does absorb strongly isstandard within Mie theory.

Both the particle and medium refractive index are in fact complexnumbers, n−ik, but in case of visible or NIR light with scattering fromwater droplets in air, the imaginary parts of both are very smallcompared to the real parts.

A dye can be added to increase the absorption or to introducefluorescence. This would give extra parameters to measure and possiblyincrease sensitivity.

In the case of fully diffused light, the most opaque aerosol is foundwhen the droplet size for a water/air mixture (mist) is between 5<x<15were Q_(pr)=0.6 is at its maximum value, as can be seen in FIG. 6. Thesize parameter is x=2πr n_(med)/λ.

This implies droplet diameters of 1.24<d<3.72 micron. In the case of lowoptical density, such as the case for the nebulizer where the opacity istypically less than 30%, single scattering only can be assumed:I=I ₀exp(−z/l _(ext))≈I ₀(1−z/l _(est))

The distance z is known, and all of the aerosol has to pass through thebeam, so small concentration differences will certainly not matter aslong as the local opacity is low enough to prevent multiple scattering.Optical absorption does not play a significant role, so the extinctionand scattering cross sections are equal (Q_(sca)=Q_(ext)).

It is straightforward to derive that l_(ext)=2d/(3f Q_(ext)).

Thus the light intensity measured by a detector in light pathconfigurations A or C:I≈I ₀(I−3f Q _(sca) z/(2d))where I₀ is the detected intensity without aerosol in the beam path. Thescattering cross section does not vary significantly over the range ofparticle diameters and is close to Q_(sca)=2.4, certainly given thedistribution of sizes.

Effectively, measuring the intensity of transmitted or backscatteredlight provides a value related to f/d, the ratio of volume fraction andparticle size.

If the particle size distribution is narrow enough, however, it ispossible to estimate any change in particle size independently from achange in aerosol volume fraction f=z d³n₀/6, where n₀=N/V (the numberdensity of particles) and N the number of particles.

This can be achieved by using quite different illumination wavelengthsλ₁ and λ₂ so that Q_(sca)(λ) has a quite different slope at the sameparticle size, for example so that x(λ₁)=13 and x(λ₂)=18. FIG. 6 showsthat these values give opposite slope in the Q_(ext)(=Q_(sca)) function.For a particle size of d=4 μm, with the size parameter beingx=πdn_(med)/λ and n_(med)=1, this would imply wavelengths ofapproximately λ₁=967 nm and λ₂=698 nm.

The invention involves the measurement of obscuration (or reflection,depending on the beam path chosen) at two or more wavelengths. Althoughin principle a tunable light source can be provided, in practice arespective light source will be provided for each selected wavelength,together with a corresponding detector tuned for detection at thecorresponding wavelength. The two (or more) wavelength measurements canbe taken simultaneously or in sequence, and they are preferably takenclose together along the aerosol flow path so that the same volumefraction and particle size are present.

The time between measurements should preferably be small enough so thatno significant movement of the aerosol has taken place. Typically thiswould be in the millisecond range.

It is possible to measure particle size absolutely if the distributionis narrow enough. If not, still a trend in change of particle size canbe observed (a shift of the distribution of particle sizes).

FIG. 6 shows that Qext is approximately equal to 2.4 in the case of abroad distribution of particle sizes as is the case for the knownnebulizer product. It is also possible to make aerosol generators thatproduce a narrow distribution, see for example the article “Miniaturizedmultiple Fourier-horn ultrasonic droplet generators for biomedicalapplications” as referenced above.

In the case of very narrow distribution of particle sizes, FIG. 6 showsthe modulation (variation in Q) on the amount of light scattering as aresult of particle size variation (changes in x). The variation Qtranslates into a variation in measured transmitted intensity I. In caseof backscattering, a similar variation will be seen, but with theopposite sign.

The use of two wavelengths means that two measurements along the sizeparameter axis are taken. By fitting the two measurements to the curve,the position along the x-axis can be derived, and thereby the particlesize d. The approximate particle size is also known from the design, aswell as the way the particle size is expected to evolve with time, andthis information can further assist in matching the measurement resultsto the curve of FIG. 6. Additional wavelengths can also be used toprovide improved mapping of the results to the theoretical plots.

Typical values for the nebulizer are:

desired particle size: d=4 μm;

wavelength chosen: λ=880 nm;

(the corresponding size parameter is x=14.3)

source-detector distance: z=14 mm

The volume fraction is equal to the fluid flow rate divided by aerosolflow rate: f=Df/Da. A typical aerosol flow rate is Da=30 l/minute and atypical fluid flow rate is Df=1 ml/minute.

The typical expected volume fraction is f≈10⁻⁵ and the typical expectedobscuration is I−I/I₀≈10⁴f≈0.1.

In FIG. 7, the aerosol particle size distribution (0.9% NaCl) is asproduced by a commercially available nebulizer (the Philips Porta Neb)and measured by a Malvern Mastersizer, which uses a HeNe laser with awavelength of λ=633 nm. The measured total obscuration is 15.8% and aD(v,0.5)=4.02 micron is found. This is a standard way to characterizeparticle distributions. The D stands for diameter, the v stands forvolume fraction and the 0.5 indicates that 50% of the particles (byvolume) and smaller than D, 4.02 micron in this case.

The detailed particle volume results have been used to calculate theobscuration for each given particle size.

FIG. 7 shows the aerosol volume fraction (“relative volume”) perparticle diameter and obscuration per particle diameter at a wavelengthof 633 nm. Experimentally, the total sum of the obscurations is 0.158 asshown by the “cumulative obscuration” plot. Each particle results insome obscuration, which can be calculated exactly by Mie theory. Thetotal obscuration is the sum of the obscuration of the individualparticles in the aerosol.

In FIG. 8, the measured aerosol particle size distribution (0.9% NaCl)is used to calculate the total obscuration as a function of wavelengthand particle size. The four plots are for different wavelength, asidentified in units of μm. It appears that the total obscuration perwavelength varies only slightly: 15.8%, 15.8% 14.9% and 11.4% forwavelengths of 405 nm, 633 nm, 880 nm and 1650 nm respectively. Thereason is that the particle distribution for the Porta Neb is too wideto show any significant resonance as a whole. From the figure it ishowever clear that such resonances do exist, i.e. for specific particlesizes, different wavelengths of light give very different obscurationmeasurement, so that a particular wavelength gives a peak obscurationlevel for a given particle size.

The above analysis shows that the obscuration will also not be verysensitive to changes in particle size, at least not through thevariation in size parameter, since the size parameter depends equally onwavelength and particle size.

In conclusion, for a wide particle distribution, the obscuration seemsmainly determined by the volume fraction of the aerosol. However, for anarrow particle size distribution, the use of multiple wavelengthsenables the determination of the particle size from a combined set ofmeasurements in transmission at different wavelengths.

Thus, if there is a wide distribution of particle sizes, the volumefraction can be derived, but if there is a narrow distribution, theactual particle size can be obtained.

Several detectors can be provided in a ring inside the mouthpiece,around the flow of aerosol. This enables measurement of the distributionof scattering angles of light in the mouthpiece. The particle size canthen be measured independently. Measurements on scattered light (such asin configuration B) are more sensitive to wavelength and particle size.In particular, looking at light scattered at larger angles, for examplenear a right angle, the contribution from large particles in thedistribution will diminish and thus enhance the visibility of smallparticles. This selection therefore narrows the effective width of thedistribution. In FIG. 8, it is clear that the small particle end of thedistribution shifts rapidly with wavelength or particle size and henceit can be used to determine the particle size more accurately.Simultaneous use of configurations A and B will help calibration andinterpretation.

Nebulizers which can be controlled by the approach of the invention canbe used for the treatment of Cystic Fibrosis, Asthma and COPD.

The invention enables optical sensing of particle size and density in anebulizer mouthpiece. The optical arrangement can also be used to derivethe aerosol flow rate, if the velocity is also obtained. As mentionedabove, a flow meter can be used for this purpose.

However, both velocity and volume flow of aerosol can be measuredoptically. To do so, the aerosol density can be measured at twopositions along the direction of flow in the mouthpiece, and thepropagation of disturbances (fluctuations) in the aerosols are monitoredand identified by cross-correlation of the signals with a variable timedelay. Hence, the average wave speed for a travelling cloud of drops canbe calculated. This is based on identifying the motion of acharacteristic signal from one detector to the next. This relies on theaerosol cloud varying over time, so that the detector signal measured isa time varying signal. The PWM control of the nebuliser already providesa signal which fluctuates over time, so that cross correlation can beused to identify when the same light detector function (with respect totime) has reached a subsequent point in the aerosol flow direction.

Feedback can be given to the driver electronics to keep any of thementioned parameters within the required bounds for proper medicaldosage.

As outlined above, the measured light can be based on light scattering,absorption or fluorescence. For absorption, use of a dye, which isharmless to the patient, can give improved contrast in the transmission.This is especially advantageous if the liquid is at low concentration,or naturally quite transparent. For fluorescence, a fluorescentmaterial, which is again harmless to the patient, is used and the lightmeasurement is at a different wavelength than that of the source. Thisis especially advantageous if the liquid has at a low concentration andthe signals may be weak or hard to distinguish from reflections orambient light. The fluorescent light typically has a longer wavelengthcompared to the excitation light, and because it is radiated in alldirections, it will be less dependent on the source-detectorpositioning. The detector then has an optical filter which passes only aband including the fluorescent light wavelength.

In all cases, the medicine or carrier thereof (usually water) mayalready have the required absorbing, scattering or fluorescentproperties, if not extra dye may be added to the formulation.

In many of the above cases, knowledge of the light scattering propertiesof the droplets is required or at least beneficial. This is provided byMie theory. Since the droplets are small, capillary forces will demandthe droplets to be spherical. This is exactly the regime where thistheory applies very accurately.

Extra information may be obtained by comparing polarized and depolarizedscattering contributions; in particular, the amount of multiplescattering can be estimated by the degree of depolarization of thelight. The ratio of scattered light polarized parallel to andperpendicularly to the linearly polarized light of the light source canbe a measure of the aerosol density, in particular if the obscuration islow. At low obscuration, single scattering (which is polarizationpreserving) is more likely, and at high density and obscuration,multiple scattering causes scrambling of the polarization.

In the examples above, light from one or more LEDs is guided from thenebulizer body through the aerosol and back onto a photo detector.However, alternative embodiments may comprise optical fibers, mirrors,integrated mirrors working on Total Internal Reflection, lenses, lasers,etc.

Look up tables can be used, for example the average speed of the dropsand liquid flux can be calculated from look-up tables, containing boththe droplet density, and said average wave speed as input parameters.

The invention uses at least two different wavelength signals fordetection. Increased accuracy may be obtained by using more than twodifferent wavelengths.

While the invention has been illustrated and described in detail in thedrawings and foregoing description, such illustration and descriptionare to be considered illustrative or exemplary and not restrictive; theinvention is not limited to the disclosed embodiments.

Other variations to the disclosed embodiments can be understood andeffected by those skilled in the art in practicing the claimedinvention, from a study of the drawings, the disclosure, and theappended claims. In the claims, the word “comprising” does not excludeother elements or steps, and the indefinite article “a” or “an” does notexclude a plurality. A single processor or other unit may fulfill thefunctions of several items recited in the claims. The mere fact thatcertain measures are recited in mutually different dependent claims doesnot indicate that a combination of these measured cannot be used toadvantage. Any reference signs in the claims should not be construed aslimiting the scope.

The invention claimed is:
 1. An aerosol measurement system, comprising:a flow device for generating an aerosol flow; a light source arrangementand a light detector for detecting light which has interacted with theaerosol flow; a controller for controlling the light source arrangementand for interpreting the detected light signals; wherein the controlleris adapted to: control the light source arrangement to provide a firstsignal at a first wavelength and to record a first detected lightsignal; control the light source arrangement to provide a second signalat a second wavelength and to record a second detected light signal;process the first and second detected signals to derive a measure of theaerosol particle size by: processing the first and second detectedsignals to determine measurements of the obscuration at each of thefirst and second wavelengths; comparing the measurements of theobscuration at each of the first and second wavelengths to a functionrelating the modulation on the amount of light scattering by an aerosolflow to particle size variation; and deriving a measure of the aerosolparticle size from the result of the comparison.
 2. A system as claimedin claim 1, wherein the light detector is for detecting light which haspassed through the aerosol flow.
 3. A system as claimed in claim 2,further comprising a dye added to an aerosol liquid.
 4. A system asclaimed in claim 1, wherein the light detector is for detecting lightwhich has been reflected or scattered by the aerosol flow.
 5. A systemas claimed in claim 4, further comprising a fluorescent additive addedto an aerosol liquid.
 6. A system as claimed in claim 1, wherein thecontroller is further adapted to derive the aerosol density from thedetected light signals.
 7. A system as claimed in claim 6, wherein thelight source arrangement comprises light sources at different positionsalong the aerosol flow, and a detector is provided for each lightsource, wherein the controller is adapted to derive the aerosol velocityfrom the detected light signals at the different positions along theaerosol flow.
 8. A system as claimed in claim 7, wherein the controlleris adapted to determine a time delay of the aerosol flow betweendifferent positions along the aerosol flow by applying a crosscorrelation to the signals received at the different positions with avariable time delay.
 9. A system as claimed in claim 1, wherein thelight detector is adapted to separate polarized and depolarized lightcontributions to determine an amount of scattering.
 10. A system asclaimed in claim 1, further comprising a flow device controller forcontrolling the flow device, wherein the system comprises a feedbackloop such that the flow device controller takes account of monitoredparameters of the aerosol flow.
 11. A method of measuring an aerosol,comprising: generating an aerosol flow; controlling a light sourcearrangement to provide a first signal at a first wavelength andrecording a first detected light signal; controlling the light sourcearrangement to provide a second signal at a second wavelength andrecording a second detected light signal; processing the first andsecond detected signals to derive a measure of the aerosol particlesize: processing the first and second detected signals to determinemeasurements of the obscuration and each of the first and secondwavelengths; comparing the measurements of the obscuration at each ofthe first and second wavelengths to function relating the modulation andthe amount of light scattering to particle size variation; and derivinga measure of the aerosol particle size from the result of thecomparison.
 12. A method as claimed in claim 11, comprising detectinglight which has passed through the aerosol flow, or detecting lightwhich has been reflected or scattered by the aerosol flow.
 13. A methodas claimed in claim 11 comprising deriving the aerosol density from thedetected light signals.
 14. A method as claimed in claim 13, comprisingderiving the aerosol velocity from the light signals at differentpositions along the aerosol flow, by applying a cross correlation to thesignals received at the different positions along the aerosol flow witha variable time delay, thereby to determine a time delay of the aerosolflow between the different positions.
 15. A method as claimed in claim11, further comprising controlling the flow device using a feedback loopwhich takes account of monitored parameters of the aerosol flow.